The role of DNA repair in protecting the cell against mutagens and carcinogens has been suggested by a variety of studies. Most of this work, however, has focused exclusively on the cytobutane pyrimidine dimer form of damage in ultraviolet (uv) irradiated DNA. The overall goal of this project is to extend our understanding of the effects of radiation and chemicals on DNA through the study and use of a damage-specific DNA binding protein isolated from human cells. This protein shows a broad specificity for monofunctional base damage in DNA, but does not recognize pyrimidine dimers, apurinic sites, single-strand breaks, single-strand regions or cross-links in DNA. As well as studying the physical and chemical properties of this protein, we have also utilized this protein as a probe to study the introduction of base damage into DNA by ionizing radiation, alkylating agents and a variety of other chemical mutagens. The role of this protein in cellular repair will be elucidated by studying its interaction with DNA-directed enzymes as well as by screening for its presence in cell lines characterized by abnormal sensitivity to radiation.